The purpose of this application is to determine the individual and cumulative effects of alcohol exposure, liver disease, and portal systemic shunting (a pre-requisite for portal systemic encephalopathy; PSE) on the neuroendocrine functioning of the hypothalamic-pituitary-gonadal axis. More specifically it is proposed to evaluate the pathogenetic role of gamma aminobutyric acid (GABA) in the syndrome of PSE and the neuroendocrine consequences of PSE with the use of an alpha and beta agonist of GABA and a GABA antagonist. Specifically the effects of alcohol, liver disease, PSE and the role of GABA in the pathogenesis of the observed alterations in LH, ACTH, and B endorphin secretion by the pituitary will be evaluated in rats in vivo and by rat pituitary and hypothalmic tissues studied in vitro. In addition, the effects of alcohol and liver disease with and without portal systemic shunting on accessory sex organ GABA- ergic ennervation and Sertoli cell secretion of transferrin and androgen binding protein will be evaluated. These studies should provide data essential to our understanding of the neuroendocrine and gonadal untoward effects of alcohol abuse, liver disease and hepatic encephalopathy. Using the data to be obtained as a result of these studies, it should be able to develop therapeutic protocols to be applied in an attempt to eliminate the common neuroendocrine abnormalities experienced by patients with alcoholism and liver disease.